Objective—To determine the prevalence of activating
internal tandem duplications (ITDs) in exons 11 and 12
of c-kit in mast cell tumors (MCTs) of dogs and to correlate
these mutations with prognosis.
Sample Population—157 formalin-fixed, paraffinembedded
MCTs from dogs in the pathology database
of the Veterinary Medical Teaching Hospital at
the University of California, Davis.
Procedure—Genomic DNA was isolated from tumor
specimens and a polymerase chain reaction procedure
was performed to determine whether there
were ITDs in exons 11 and 12.
Results—We identified ITDs in 1 of 12 (8%) grade-I,
42 of 119 (35%) grade-II, and 9 of 26 (35%) grade-III
tumors (overall prevalence, 52 of 157 [33%]). Logistic
regression analysis revealed that the odds of grade-II
and -III tumors possessing an ITD were approximately
5 times greater than that for grade-I tumors,
although these odds did not differ significantly.
Although MCTs possessing an ITD were twice as likely
to recur after excision and twice as likely to result
in metastasis as those without an ITD, these values
also did not differ significantly.
Conclusions and Clinical Relevance—These results
provide evidence that ITDs in c-kit occur frequently in
MCTs of dogs. The high prevalence of c-kit activating
mutations in MCTs of dogs combined with the relative
abundance of mast cell disease in dogs provide
an ideal naturally developing tumor in which to test
the safety and efficacy of novel small-molecule kinase
inhibitors such as imatinib mesylate. (Am J Vet Res
Objective—To evaluate safety and efficacy of LDI-100, a preparation containing human chorionic gonadotropin (hCG) and bacillus Calmette-Guerin (BCG), in the treatment of dogs with mast cell tumors and to compare results with those from a control group receiving single-agent vinblastine.
Animals—95 dogs with measurable grade II or III mast cell tumors.
Procedures—Dogs were randomized to receive either LDI-100 (1.35 ng of BCG and 2 units of hCG, SC, q 24 h) or vinblastine (2 mg/m2, IV, q 1 wk) for 6 weeks. Tumors were measured at baseline and day 42, and dogs were monitored for signs of toxicosis. Clinical performance scores were recorded at each visit. Differences in host factors (sex, weight, and age), clinical performance score, tumor response, and adverse events were analyzed.
Results—46 dogs received LDI-100, and 49 dogs received vinblastine. No significant differences were found between the 2 treatment groups with regard to host factors or clinical performance score. Tumor response (≥50% reduction) rates were similar between the LDI-100 and vinblastine group (28.6% and 11.7%, respectively). Dogs in the LDI-100 group had significantly less neutropenia than the vinblastine group.
Conclusions and Clinical Relevance—hCG and BCG have immunomodulatory and antitumor effects against a variety of malignancies in humans and dogs. In this study, LDI-100 provided clinical responses comparable to single-agent vinblastine chemotherapy but without myelosuppression. LDI-100 is a promising new agent that should be further investigated for multimodality therapy of mast cell tumors in dogs.